We propose to continue our investigation of the neuropharmacological aspects of the actions and abuse potential of enkephalins, endorphins and other endogenous "opioid-like" substances. We will follow the advice of the critique from the review of a previous application and focus our efforts on two of the observations made during the first two years of this grant. We propose to continue the investigation of the release of endogenous opiates into cerebrospinal fluid following the administration of morphine and other antinociceptive manipulations including, other drugs, stress and acupuncture. The isolation of the endogenous opiates by high pressure liquid chromatography and other chromatographic techniques and the quantification of the material by radioimmunoassay and bioassay is an important part of our research plan. Another aspect of these investigations will be to use similar techniques for the investigation of changes in opiate like material in brain induced by antinociceptive agents and manipulations. A continuation of our comparision of the neuropharmacology, and neurophysiological effects and the abuse potential of methionine-enkephalin, the more stable D-ala2-Nle5-enkephalin and beta endorphin is the second major aspect of this research proposal.